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JCI Insight. 2017 Jun 15;2(12). pii: 92295. doi: 10.1172/jci.insight.92295. eCollection 2017 Jun 15.

α-Synuclein in gut endocrine cells and its implications for Parkinson's disease.

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Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina, USA.
Department of Pathology and.
Department of Medicine, UCSF, San Francisco, California, USA.
Invitae Corporation, San Francisco, California, USA.
Duke Institute for Brain Sciences, Durham, North Carolina, USA.


Parkinson's disease (PD) is a progressive neurodegenerative disease with devastating clinical manifestations. In PD, neuronal death is associated with intracellular aggregates of the neuronal protein α-synuclein known as Lewy bodies. Although the cause of sporadic PD is not well understood, abundant clinical and pathological evidence show that misfolded α-synuclein is found in enteric nerves before it appears in the brain. This suggests a model in which PD pathology originates in the gut and spreads to the central nervous system via cell-to-cell prion-like propagation, such that transfer of misfolded α-synuclein initiates misfolding of native α-synuclein in recipient cells. We recently discovered that enteroendocrine cells (EECs), which are part of the gut epithelium and directly face the gut lumen, also possess many neuron-like properties and connect to enteric nerves. In this report, we demonstrate that α-synuclein is expressed in the EEC line, STC-1, and native EECs of mouse and human intestine. Furthermore, α-synuclein-containing EECs directly connect to α-synuclein-containing nerves, forming a neural circuit between the gut and the nervous system in which toxins or other environmental influences in the gut lumen could affect α-synuclein folding in the EECs, thereby beginning a process by which misfolded α-synuclein could propagate from the gut epithelium to the brain.


Gastroenterology; Neuroscience

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